Cancer is a broad group of various diseases, all involving unregulated cell growth without mortality, as a result of the abnormal differentiation or proliferation induced by the modification of the structural and functional unit cells. In cancer, cells invade nearby parts of the body, and may also spread to more distant parts of the body through the lymphatic system or bloodstream, and finally metastasize to other organs such as the lung, and the liver. There are over 100 different known cancers that afflict humans. Representative among them are lung cancer, colorectal cancer, stomach cancer, and liver cancer. As a rule, the risk of developing cancer generally increases with age, and there is an upward tendency in the onset of cancer worldwide since the average life of man's life has been increased. However, an effective cure for cancer has not yet been found, and thus, there is a pressing need for novel cancer treatments. Cancer is usually treated with surgery, chemotherapy, and radiation therapy. These treatments, however, may provoke significant side effects including the onset of secondary cancer, the metastasis of cancer, immune suppression, and aberrant cellular metabolisms. In consideration of problems with conventional cancer treatments, taking advantage of the immune system of patients is an idea drawing intensive attention as a potential strategy for the development of cancer therapies. The development of cancer vaccines is one of the most desirable medical approaches.
Designed to evoke potent immune responses to cancer, a cancer vaccine activates the immune mechanism of patients so as to enhance resistance to cancer. Cancer vaccination is advantageous in that it causes few side effects and it helps the immune system of patients to fight the cancer that remains even after surgery, as well as metastasized, invisible cancer, by itself. When account is taken of the fact that most cancers are generated by the modification of autologous cells, it is important for successful cancer vaccine development to select proper cancer antigens that induce the immune system of a patient to recognize cancer as an attack target. For use as a cancer antigen, a peptide or a protein that is already known to act as an antigen may be separated from cancer cells, or cancer cells themselves may be applied after treatment with radiation. These cancer antigens may be used in combination with an adjuvant or loaded to dendritic cells in order to enhance immune reactions. It is easy to prepare peptide or protein antigens if they are already known, but they may cause immune tolerance, because proper antigens differ from one patient to another. Cancer is considerably heterogeneous, and cancer-specific antigens are difficult to define. In addition, patients are different from each other in terms of cancer etiology and immunity control mechanism. Accordingly, a standardized treatment cannot guarantee success in the therapy of cancer. If obtained by surgery, a tumor tissue from a cancer patient may be used as a source of various cancer antigens specific for the patient. The use of cancer cells themselves, however, may evoke side effects including the risk of oncogenesis and autoimmune responses. There is therefore a need for a tumor-derived cancer vaccine that is of high utility and safety.
Nano-sized vesicles may be used as an antigen in cancer vaccination. Nano-sized vesicular antigens can be easily recognized and captured by antigen-presenting cells such as dendritic cells, and readily circulated through the lymphatic system, so that they are highly apt to induce immune responses. Representative of nano-sized vesicles are extracellular vesicles (e.g., exosomes, microvesicles, etc.) that spontaneously shed from almost all cell types. Extracellular vesicles range in size from tens to hundreds nm, and consist of a bilayer lipid membrane, with biologically active materials, such as proteins, lipids and genetic materials, contained therein, performing various physiological/pathological functions. Particularly, if originating directly from the plasma membrane of cancer cells, the extracellular vesicles reflect the antigenic content of the cancer cells. Further, cancer cell-derived extracellular vesicles contain high local concentrations of cancer antigens because of their high surface-area-to-volume, and are more apt to induce immunization, compared to an antigen in a receptor form. Moreover, extracellular vesicles may be used as a cell-free vaccine and thus are expected to cause significantly fewer side effects, compared to conventional tumor cell vaccines for which it is difficult to obtain clinical permission.
However, extracellular vesicles are disadvantageous in practical clinical application for the following reasons. A cell line of cancer cells separated directly from patients must be established in order to obtain extracellular vesicles therefrom. It is difficult to secure extracellular vesicles in a large quantity because they are released in a trace amount. Intricate separation and purification of extracellular vesicles requires high expense and much time. Therefore, nanovesicular antigens need to be developed as an alternative to tumor-derived extracellular vesicles.